The invention relates both to the testing and evaluation of biological and non-biologic substances, electrical elements and electrochemical element, and combinations thereof, that are responsive to electrical excitation, as well as to the control of systems incorporating such substances and/or electrical and electrochemical elements, each of which exhibits the general characteristic of impedance, or conversely, admittance. A Device Under Test (D.U.T.), which may be, or may contain, any combination of substance or elements, is excited with a time-varying electrical signal while a synchronous sampling means is employed to acquire the response. A variety of analyses may be performed on the acquired data to determine at least one characteristic of the D.U.T.; in alternate embodiments, the inventive method may be used to assist or control systems within which said substances are either removably or permanently incorporated.
The determination of characteristics of electrically responsive elements and substances may be accomplished using both Frequency Domain and Time Domain techniques, commonly know as Frequency Response Analysis and Time Domain Spectroscopy respectively.
In the discussion that follows, the application of the inventive method both to simple non-biologic systems such as a non-rechargeable electrochemical accumulator (conventionally referred to as a “cell” or battery of cells), and to complex biologic systems, such as chemical samples derived from living organisms, will be described.
Lithium sulfur dioxide cells (LiSO2) exhibit a 2.95V nominal operating voltage and provide high energy density and a relatively flat discharge profile over a wide temperature range. This combination of low weight per watt and excellent discharge characteristics make them the cell of choice for mission critical applications. The flat cell voltage profile, which makes such cells desirable, also presents difficulties in determining cell condition and state of charge.
Attempts have been made to use frequency response analysis, or electrochemical impedance spectroscopy techniques to evaluate these cells. However, the static impedance profile of this cell remains virtually flat across a wide range of test frequencies until nearly the end of their useful service life. In addition, to obtain a reasonable impedance/frequency profile using FRA techniques, sophisticated measuring equipment is used to provide multiple (sequential) tests at a plurality of frequencies, resulting in severely protracted test times.
Traditional chronopotentiometry/chronoamperometry (both conventional and cyclic) offer another method of measuring electrochemical cells. Here, the cell is provided with an excitation signal and the time varying response of the cell is determined. Traditional methods employ excitations (current or voltage) such as ‘constant value’ or ‘pulse followed by relaxation interval’. One commercially available lithium battery tester employs such a ‘pulse discharge/relaxation’ method. It provides a relatively high current discharge event (60 seconds, at about a C1-hr-rate/4), followed by a ‘rest’ period, wherein the battery is placed on open-circuit, and uses the profile of the battery's recovery voltage to diagnose the state of charge. With this device, when severely depleted batteries are tested, the high current levels employed can occasionally lead to ‘venting’ of SO2 gas, with the attendant possibility of cell rupture. In addition, multiple, sequential tests of the same battery are strongly discouraged.
When evaluating the electrical response of a biologic target substance, multiple problems may arise as well. For example, currently a variety of well-known electrochemical techniques exist for performing assays of biological material. These techniques may be separated into three primary categories: 1) passive techniques or methods, 2) active techniques or methods and 3) a combination of passive and active techniques or methods; each of these is discussed in more detail below.
The application of a passive assay technique typically involves disposing one or more components within a test environment so that a chemical or electrochemical reaction occurs and gives rise to a detectable (measurable) current or voltage output.
The application of an active assay technique typically involves placing the substance of interest (henceforth, the “analyte”) within a test chamber equipped with at least two electrodes. The analyte(s), which may be a single substance or some combination of different substances, is then excited, via the electrodes, with either a voltage or a current. The resultant conjugate response, which will take the form of a current or voltage respectively, may then be measured. In well-designed test paradigms, the nature or characteristics of the substance of interest (e.g., the “analyte”) may be inferred from the functional and/or dynamical relationship that obtains between the excitation and the response signals.
These active techniques may be further separated into a plurality of sub-categories depending upon the nature of the excitation employed. If the assay technique employs a voltage which is applied across the excitation probes (i.e. ‘across’ the specimen disposed within the test chamber) as the independent variable and the voltage is constant, the active assay technique may be referred to as potentiostatic, whereas if the voltage is time-varying, the active assay technique may be referred to as potentiodynamic. As an example, U.S. Pat. No. 5,871,918 to Thorpe discloses a voltage-mode test method wherein cyclic voltammetry is employed to detect the presence of specific nucleic acids in a test sample. However, if the assay technique employs a current which is applied across the excitation probes (i.e. ‘across’ the specimen disposed within the test chamber) as the independent variable and the current is fixed or constant, the active assay technique may be referred to as galvanostatic, whereas if the current is time-varying, the active assay technique may be referred to as galvanodynamic.
Moreover, these methods may be employed in combination with each other. The application of a combination of the active and passive techniques typically employs an experimental paradigm, which may combine two or more of these techniques or methods in sequence. For example, a constant current may be forced through a test chamber until a specified differential voltage appears across the chemical sample, whereby the excitation control method abruptly changes to a ‘constant voltage’ mode, wherein the current is adjusted to maintain that specific voltage differential. The resultant time-varying current thereafter becomes the dependent (measured) variable. Additional alternations between voltage-mode and current-mode excitation control may also be incorporated into the experimental paradigm as well.
While current-mode excitation techniques have been used extensively in several areas related to biochemistry, these techniques are used primarily for the modification of biological systems rather than as the basis of analysis or measurement methods. As an example, U.S. Pat. No. 4,663,006 refers to the remediation of blood chemistry imbalance regarding a method of electrochemical dialysis employing alternating current excitation and electro-mediated osteogenesis.